To date, tele-methylhistamine, the product of enzymatic histamine methylation, has not been measured by a suitable method. Tele- and pros-methylhistamine both react quantitatively with trifluoroacetic and heptafluorobutyric anhydrides at room temperature under anhydrous conditions to yield either mono-or bis-derivatives in the absence or presence of pyridine, respectively. The extraction of tissue homogenates, derivatization, and analysis by gas chromatography-mass fragmentography permits the detection of 1 ng/ml tele-methylhistamine, using pros-methylhistamine as the internal standard. Rat brain contains tele-methylhistamine in a concentration similar to that of histamine (42 ng/g). The content of this amine in tissue has been compared with that obtained by other methods. © 1979.